Synthesis of wound hormone



Patented Dec. 25, 1945- UNITED STATES PATENT OFFICE SYNTHESIS OF WOUND HORMONE tion of California No Dra Original application November 30,

wing 1940. Serial No. 367,950. Divided and this application January 11, 1944, Serial No. 517,838

3 Claims. (Cl- 260-485) This application is a division oi our co-pendlns agzication Serial No. 367.950, filed November 30, 1

This invention relates to processes tor the synthesis of certain wound hormones and to intermediates for use in such synthesis.

Many plant tissue extracts are capable of inducing renewed growth activity in mature plant cells. These growth-inducing extracts are usually obtained from ground or heated tissues and they are capable of evoking cell division and cell enlargement in unwounded cells. Such active principles have been termed wound hormones."

The present application is concerned more particulariy with the synthetic production of l-decene-LlO-dicarboxylic acid, which substance has been found to be highly active in stimulating the process oi healing wounds in plant tissue.

We have found that l-decene-LlO-dicarboxylic acid may be synthesized by converting undecylenic acid or alkyl esters thereof to the hall. aldehyde oi sebacic acid, or its alkyl ester, by treatment with a highly active oxidizing agent, such as ozone, for example. The oxidation product is then condensed with malonic acid in the presence of an inert tertiary amine, such as pyridine. to give the corresponding l,lo-dicarboxy-decene-l. or l-carboxy-lO-carbalkoxy-decene-l. If the ester aro p is present, it may be hydrolyzed of! by heating in alkaline medium, and, after acidification, the desired acid is obtained. This series of reactions is outlined in the following flow sheet in which the process is illustrated in terms of methyl undecylenate:

cmooc-(cm ,on=om .21,

Melanie omooc-(cnmcno H Py dine mamas: cn.ooo-(cm)-on=on-coon HOOC-(CHl)iCH=CH-OOOH n In the examples given below a specific method of carrying out our invention is given. It is to be understood, however, that modifications may bemade thereinbythossskilledintheartwithout departing from the spirit and scope of our invention.

Example I Undeeylenic acid methyl ester (B. P. 119-120" 0., mm.) is ozonized in acetic acid solution to the hali aldehyde oi methyl sebacate (B. P. 124- 125 0. (4. mm.)].

mixed with ms. of malonic acid and 15 gms.

I of dry pyridine and heated under reflux for four hours. A vigorous evolution or carbon dioxide occurs in the early stages of the reaction. The resulting clear solution is acidified, poured into water, and extracted with ether. After removal of the pyridine by extraction with dilute hydrochloric acid, the ether is evaporated and the crude product hydrolyzed directly by heating under reflux with three normal sodium hydroxide for two hours. Upon acidification, the 1-decene-1,10-dicarboxylic acid precipitates and is recrystallized from alcohol or acetone, M. P. 165-166 C.

An oxidation or the synthetic product with permanganate in hot water solution gave sebacic acid, identified by melting point (133") and mixed melting point.

Example 11 Undecylenic acid ethyl ester is treated as in 2 Example I. l-carboxy-lO-carbethoxy-decen-l is obtained as an intermediate. After alkaline hydrolysis and acidification, l-decene-LiO-dicarboxylic acid is obtained.

Example III Undecylenic acid butyl ester is treated as in Example I. l-carboxy-io-carbbutom-decene-l is obtained as an intermediate. Aiter alkaline hydrolysis and acidification, 1-decene-1,l0-diso carboxylic acid is obtained.

hydrolysis and acidification, l-decene-LlO-di.

carbonilc acid is obtained.

Esample V Undecylenic acid isopropyl ester is treated as in Example I. l-carboxy-lo-carbisopropoxy-deoene-i is obtained as an intermediate. After alkaline hydrolysis and acidification, l-decene-1,10- dicarboxylic acid is obtained.

Example VI Undecylenic acid is treated according to the process of Example I. l-decene-l.l0-dicarboxylic acidisobtained directly.

We claim:

so 1. A l-carboxy-lO-carbalkoxy-decene-l.

lalmaofthlaplomls 2. l-carboxy-lO-csrbmethoxy-decene-l.

8. l-carboxy-lO-carbethoxy-decene-l.

JAMES ENGLISH, JR. JAMES BONNER. A. J. HAAGEN-Blll'l'. 

